PPARγ and retinol binding protein 7 form a regulatory hub promoting antioxidant properties of the endothelium

Abstract

Peroxisome proliferator-activated receptors (PPARs) are a family of conserved ligand-activated nuclear receptor transcription factors heterogeneously expressed in mammalian tissues. PPARγ is recognized as a master regulator of adipogenesis, fatty acid metabolism, and glucose homeostasis, but genetic evidence also supports the concept that PPARγ regulates the cardiovascular system, particularly vascular function and blood pressure. There is now compelling evidence that the beneficial blood pressure-lowering effects of PPARγ activation are due to its activity in vascular smooth muscle and endothelium, through its modulation of nitric oxide-dependent vasomotor function. Endothelial PPARγ regulates the production and bioavailability of nitric oxide, while PPARγ in the smooth muscle regulates the vasomotor response to nitric oxide. We recently identified retinol binding protein 7 (RBP7) as a PPARγ target gene that is specifically and selectively expressed in the endothelium. In this review, we will discuss the evidence that RBP7 is required to mediate the antioxidant effects of PPARγ and mediate PPARγ target gene selectivity in the endothelium.